Long spinal axons of primary sensory neurons can grow into peripheral nerve grafts and this regeneration is enhanced one hundred-fold by transection of the peripheral axons at the time of grafting. The endoneurial event that triggers the enhancement could be either release of an injury factor or interruption of retrograde transport of a normal regulatory agent. In the latter context, an attempt will be made to replicate the transganglionic induction of regeneration by intraneural injection of colchicine to block retrograde axoplasmic transport. To test specifically the possible importance of perikaryal deprivation of nerve growth factor in this phenomenon, nerve growth factor will be delivered by osmotic pump to cut nerves of grafted rats and a mitigation of induction will be sought. Other experiments will analyze the inductive effects of several different nerve injuries and will investigate an observation that the glial environment at the site of grafting loses its ability to support axon growth in time. Finally, the effects of sciatic nerve transection on regeneration in lumbar dorsal spinal roots will be studied. This application concentrates on glial influences in regeneration and on neuronal reactions to injury of their axons. A long term aim is to be able to modify therapeutically the degeneration and regeneration of injured neurons.